Compositions and kits for the removal of irritating compounds from bodily surfaces

ABSTRACT

The invention provides compositions, methods and kits for the removal of harmful or irritating substances from bodily surfaces. Kits may include a composition containing capsaicin and a capsaicin-cleansing composition, e.g., a composition in which capsaicin is soluble.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a divisional application of U.S. application Ser.No. 14/542,041, filed on Nov. 14, 2014, which is a continuation of U.S.application Ser. No. 13/596,773, filed on Aug. 28, 2012, now U.S. Pat.No. 8,889,113, which is a continuation of U.S. application Ser. No.12/830,997, filed on Jul. 6, 2010, now U.S. Pat. No. 8,263,059, which isa continuation of U.S. application Ser. No. 10/655,911, filed Sep. 5,2003, now abandoned, which claims the benefit of U.S. Provisional PatentApplication Nos. 60/408,751, filed Sep. 5, 2002, and 60/410,616, filedSep. 13, 2002, each of which is hereby incorporated by reference intheir entirety.

TECHNICAL FIELD

The invention relates to kits, compositions, and methods for the removalof harmful or irritating substances from bodily surfaces, in particularto kits containing a composition containing capsaicin or a capsaicinanalog and a capsaicin-cleansing composition. Such kits and compositionsfind application in medicine and animal health.

BACKGROUND OF THE INVENTION

Many compounds are irritating or painful when contacted with bodilysurfaces. Examples include urushiols, which are constituents of poisonoak, poison ivy, poison sumac, and other oily plant resins withirritating properties. Another example is capsaicin. Capsaicin is aconstituent of pepper sprays, and capsaicin and its analogs are used intopical form for pain relief. Even at low concentrations (e.g., 0.075%by weight) capsaicin preparations can cause burning pain andhyperalgesia. This is the effect sought in pepper sprays, and is a sideeffect of therapeutic treatments of pain. At higher capsaicinconcentrations used for the treatment of some intractable painconditions, the initial pain accompanying application of capsaicin istreated by anesthesia (see, e.g., U.S. Pat. Nos. 6,248,788 and6,239,180).

BRIEF SUMMARY OF THE INVENTION

One aspect of the invention provides a kit that includes a first deviceor composition containing capsaicin or a capsaicin analog; and a seconddevice or composition containing a substance in which capsaicin issoluble, wherein the first and second devices or compositions areseparately packaged. In some embodiments, the second composition is acomposition in which capsaicin has a solubility of at least about 10percent w/w. In some embodiments, the second composition is acomposition in which capsaicin has a solubility of at least about 20percent w/w. In some embodiments, the second composition is acomposition in which capsaicin has a solubility of at least about 25percent w/w. The compositions are useful for effectively removingcapsaicin and other irritating or painful resinous or oily substancesfrom bodily surfaces quickly and effectively in order to minimize painand irritation from the substances. In certain embodiments, the firstcomposition of the kit may include capsaicin or a capsaicin analog in anamount sufficient to treat a capsaicin-responsive condition (e.g., atherapeutically effective amount), for example, a concentration betweenabout 0.001 to about 60 percent w/w, e.g., about 0.001 to about 1percent w/w, or about 0.1 to about 15 percent w/w or about 1 to about 10percent w/w; for example, about 5 to about 10 percent w/w. In someembodiments, the capsaicin or capsaicin analog is contained in a spray,lotion, emulsion, liniment, or gel. In other embodiments, the capsaicinor capsaicin analog is contained in a transdermal patch. In one suchembodiment, the capsaicin or capsaicin analog is present in thetransdermal patch at an amount of about 0.64 mg/cm². In some embodimentsof this aspect of the invention, the second composition of the kitcontains polyethylene glycol and a polyacrylate thickening polymer. Insome embodiments, the second composition of the kit contains about 60 toabout 99 percent w/w polyethylene glycol (PEG); about 0.1 to about 4.0percent w/w polyacrylate thickening agent; and the balance water;wherein the composition is at a pH between about 6.0 and about 8.0. Insome embodiments, the second composition of the kit contains about 84 toabout 94 percent w/w polyethylene glycol; about 0.1 to about 2 percentw/w polyacrylate thickening agent; and the balance water; wherein thecomposition is at a pH of about 7.0 to 7.5. In further embodiments ofthis aspect of the invention, the second composition of the kit maycontain, in addition to PEG and a polyacrylate thickener, about 0.005 toabout 0.05 percent w/w butylated hydroxyanisole; and about 0.05 to about0.5 percent w/w EDTA/EDTA salts.

In some embodiments, the kit includes a third composition comprising ananesthetic.

Kits of the invention may also include instructions for use of thecapsaicin composition and the cleansing composition.

In one aspect, the invention provides a kit comprising a transdermalpatch comprising capsaicin and a capsaicin cleansing gel. The kit mayalso provide an anesthetic. For example, in one embodiment, thetransdermal patch contains capsaicin at an amount of about 0.64 mg/cm²;a cleansing gel containing about 84 to about 94 percent w/w polyethyleneglycol, about 0.1 to about 2 percent w/w polyacrylate thickening agent,about 0.005 to about 0.05 percent w/w butylated hydroxyanisole, about0.05 to about 0.5 percent w/w EDTA/EDTA salts, and the balance water;wherein the second composition is at a pH of about 7.0 to 7.7; and acomposition comprising an anesthetic. This embodiment may furthercontain instructions for use.

In another aspect, the present invention provides a composition forcleansing a bodily surface. In embodiments, the invention providescomposition in which capsaicin has a solubility of at least about 10%w/w, or at least about 20% w/w, or at least about 25% w/w. Someembodiments of compositions provided by the invention include acomponent in which capsaicin is soluble, e.g., a component in whichcapsaicin is soluble to greater than about 10% w/w, greater than about20% w/w, or greater than about 25% w/w, and a thickening agent. In oneembodiment, a composition of the invention contains about 60 to about 99percent w/w polyethylene glycol (PEG, e.g., PEG 300). In one embodiment,a composition of the invention contains about 60 to about 99 percent w/wpolyethylene glycol (PEG, e.g., PEG 300), about 0.1 to about 4 percentw/w thickening agent, and the balance water; wherein the composition isat a pH between about 6.0 and about 8.0. The thickening agent can be apolyacrylate. In another embodiment, the composition includes about 84to about 94 percent w/w polyethylene glycol (PEG, e.g., PEG 300); about0.1 to about 2 percent w/w polyacrylate thickening agent; and thebalance water; wherein the composition is at a pH between about 7.0 andabout 7.7. In a further embodiment, the composition includes about 88 toabout 92 percent w/w polyethylene glycol (PEG, e.g., PEG 300); about 0.1to about 2 percent w/w polyacrylate thickening agent; and the balancewater; wherein the composition is at a pH between about 7.0 and about7.7. In yet a further embodiment, the composition includes about 90percent w/w polyethylene glycol (PEG, e.g., PEG 300); about 0.1 to about2 percent w/w polyacrylate thickening agent; and the balance water;wherein the composition is at a pH between about 7.0 and about 7.7. Instill another embodiment, the composition includes about 84 to about 94percent w/w polyethylene glycol (PEG, e.g., PEG 300); about 0.3 to about1.5 percent w/w polyacrylate thickening agent; and the balance water;wherein the composition is at a pH between about 7.0 and about 7.7. Instill yet another embodiment, the composition includes about 84 to about94 percent w/w polyethylene glycol (PEG, e.g., PEG 300); about 1.0percent w/w polyacrylate thickening agent; and the balance water;wherein the composition is at a pH between about 7.0 and about 7.7. Insome embodiments of the invention, the polyethylene glycol comprises PEG200 or PEG 300.

Compositions of the invention may also contain, in addition to PEG and athickening agent, stabilizer(s). In some embodiments, stabilizers of theinvention include about 0.005 to about 0.05 percent w/w butylatedhydroxyanisole; and about 0.05 to about 0.5 percent w/w EDTA/EDTA salts.Some embodiments that include stabilizers may include about 87 to about91 percent w/w polyethylene glycol; about 0.3 to about 1.5 percent w/wpolyacrylate thickening agent; about 0.01 to about 0.03 percent w/wbutylated hydroxyanisole; about 0.02 to about 0.2 percent w/w EDTA/EDTAsalts; and the balance water; wherein the composition is at a pH ofabout 7.0 to about 7.7. A further embodiment includes about 89.08percent w/w PEG 300; about 1.0 percent w/w polyacrylate thickeningagent; about 0.02 percent w/w butylated hydroxyanisole; about 0.1percent w/w EDTA/EDTA salts; and the balance water; wherein thecomposition is at a pH of about 7.5.

In another aspect, the invention includes an article of manufacture forcleansing a bodily surface including (a) a composition containing about84 to about 94 percent w/w polyethylene glycol (PEG); about 0.1 to about2.0 percent w/w polyacrylate thickening agent; and the balance water;wherein the composition is at a pH between about 7.0 and about 7.7; and(b) a container suitable for dispensing the composition of (a); whereeither the container is labeled with instructions for the use of thecomposition of (a), or the article of manufacture includes separateinstructions for the use of the composition of (a).

Yet another aspect of the invention includes a method for cleansing abodily surface that has been contacted with an irritating or painfulsubstance. In some embodiments, the method includes the steps of (a)applying to the bodily surface a composition in which capsaicin has asolubility of at least about 10% w/w, or at least about 20% w/w, or atleast about 25% w/w.; and (b) removing the composition of step (a) fromthe bodily surface. In some embodiments, the method includes the stepsof (a) applying to the bodily surface a composition that contains about60 to about 99 percent w/w polyethylene glycol (PEG, e.g., PEG 300); and(b) removing the composition of step (a) from the bodily surface. Insome embodiments, the method includes the steps of (a) applying to thebodily surface a composition that contains about 60 to about 99 percentw/w polyethylene glycol (PEG, e.g., PEG 300), about 0.1 to about 4percent w/w thickening agent, and the balance water; wherein thecomposition is at a pH between about 6.0 and about 8.0.; and (b)removing the composition of step (a) from the bodily surface. In someembodiments, the method includes the steps of (a) applying to the bodilysurface a composition containing about 80 to about 99 percent w/wpolyethylene glycol, about 0.1 to about 2 percent w/w polyacrylatethickening agent and the balance water; wherein the composition is at apH of about 7.0 to about 7.7; and (b) removing the composition of step(a) from the bodily surface. In other embodiment, the method includesthe steps of (a) applying to the bodily surface a composition containingabout 87 to about 91 percent w/w polyethylene glycol, about 0.3 to about1.5 percent w/w polyacrylate thickening agent, about 0.01 to about 0.03percent w/w butylated hydroxyanisole, about 0.02 to about 0.2 percentw/w EDTA/EDTA salts and the balance water; wherein the composition is ata pH of about 7.0 to about 7.7; and (b) removing the composition of step(a) from the bodily surface.

Yet a further aspect of the invention includes a method for treating anindividual suffering from a capsaicin-responsive condition. In oneembodiment, the invention provides a method for treating pain in anindividual, including the steps of (a) applying a composition containingcapsaicin or a capsaicin analog to the painful area; and (b) cleansingbodily surfaces that have been exposed to capsaicin by applying to thebodily surfaces a composition comprising a component in which capsaicinhas a solubility of greater than 10% w/w, or greater than 20% w/w, orgreater than 25% w/w; and removing said composition from the area. Insome embodiments of this aspect of the invention, the capsaicin orcapsaicin analog is present in the capsaicin-containing composition in atotal concentration greater than about 5% by weight. In some embodimentsof this aspect of the invention, step (a) of the method includesaffixing to the affected area a skin-adherent patch, the patch includinga reservoir containing a therapeutic formulation whereby saidformulation is provided to the surface of the skin, and where theformulation contains capsaicin or a capsaicin analog in a totalconcentration from greater than about 5% to 10% by weight of theformulation. In some embodiments of this aspect of the invention, themethod further includes, in addition to applying capsaicin or capsaicinanalogs and removing the capsaicin or capsaicin analogs, administeringan anesthetic to the individual in whom pain is to be treated, prior tothe application of the capsaicin or capsaicin analog. In some of theseembodiments, the anesthetic is administered in the form of an afferentnerve block.

BRIEF DESCRIPTION OF THE DRAWING

FIG. 1 illustrates schematically the manufacturing process for acleansing solution.

DETAILED DESCRIPTION OF THE INVENTION

The invention provides kits that contain a component containingcapsaicin or a capsaicin analog, and another component for cleansingcapsaicin or a capsaicin analog, and methods for their use. Theinvention also provides compositions useful for cleansing skin and otherbodily surfaces, e.g., eyes and mucous membranes, that have been exposedto painful or irritating compounds, and methods for their use.

In one aspect, the invention provides kits that include a compositioncontaining capsaicin or a capsaicin analog together with a capsaicincleansing composition in which capsaicin or a capsaicin analog issoluble. In some embodiments, capsaicin or the capsaicin analog issoluble to at least about 10% w/w, at least about 20% w/w, or at leastabout 25% w/w in the capsaicin cleansing composition. The kits mayfurther include a composition containing an anesthetic, instructions,and other optional components.

In one aspect the invention provides compositions for cleansing skin andother bodily surfaces that have been exposed to a painful or irritatingsubstance, e.g., capsaicin or a capsaicin analog. In embodiments, theinvention provides compositions in which capsaicin is soluble, e.g., inwhich capsaicin has a high solubility, that are non-toxic, and that areeasy to apply and to remove. In an embodiment, the compositions do notreadily penetrate the skin. In some embodiments the compositions containpolyethylene glycol, a polyacrylate thickening agent, and water, at a pHsuitable for topical use. In some embodiments, the compositions may alsocontain preservatives such as an antioxidant and a chelating agent. Thecompositions may be applied to bodily surfaces exposed to capsaicin orother painful or irritating compounds, e.g., by a tissue impregnatedwith the composition, then wiped off the bodily surface, to neutralizethe irritating effect of the compound, e.g., capsaicin, on the eyes,skin, fascia, and mucous membranes.

In a further aspect, the invention provides methods for removingirritating or painful substances from bodily surfaces by applying thecompositions of the invention to the bodily surface, then removing them.In a yet further aspect, the invention provides methods for treating acapsaicin-responsive condition by applying capsaicin or a capsaicinanalog to a bodily surface, then removing excess capsaicin or capsaicinanalog. In some of these embodiments, the capsaicin-responsive conditionis pain.

All percentages and ratios used herein are by weight of the totalcomposition (i.e., w/w), and all measurements made are at 25° C., unlessotherwise designated.

I. COMPOSITIONS

Compositions provided herein include a first component in whichcapsaicin and its analogs are soluble, e.g., have high solubility. Insome embodiments the compositions include a second component that actsas a thickening agent, and water. If necessary, the pH is modified by asuitable pH modifier to a range appropriate for application to bodilysurfaces, i.e., non-harmful and non-irritating pH. In some embodimentsthe composition also includes stabilizers and/or other components. Insome embodiments, the composition contains polyethylene glycol at highconcentration and CARBOPOL 1382™ or similar carbomer or thickeningagent, optionally including BHA and EDTA/EDTA salts. In someembodiments, the compositions contain polyethylene glycol, apolyacrylate thickener, and water, and are substantially free of othercomponents.

In some embodiments of the invention, the cleansing composition issubstantially free of surfactant and/or particulates. By “substantiallyfree” is meant that no surfactant and/or particulate is added to thecomposition, and any such components are present, if at all, only astrace impurities. These embodiments particularly lend themselves toremoval of capsaicin from exposed bodily surfaces, because the surfaceis already extremely sensitive due to a pre-existing medical conditionand any additional irritation from particulate, surfactant, or otheradditives is undesirable. Surprisingly, despite the lack of particulatesand surfactant to assist in reaching irregularities of the skin and toassist in cleansing oily components, the compositions of the inventionthoroughly cleanse bodily surfaces of capsaicin. The compositions of theinvention may also be used for removal of other agents from bodilysurfaces, e.g., toxins (e.g., pesticides, animal toxins), householdchemicals (e.g., paint, varnish), and the like. As shown in Example 6,components of the cleansing solution typically do not penetrate thestratum corneum. For illustration and not limitation, various aspects ofthe compositions will be described in greater detail.

A. Capsaicin-Solubilizing Agent

Provided are compositions that can be applied to a bodily surface thathas been exposed to an irritating or painful substance. Thesecompositions may be described herein as “cleansing compositions” and,when the irritating or painful substance is capsaicin,“capsaicin-cleansing compositions.” As used herein, a composition“cleanses” a bodily surface of a painful or irritating substance, or isa “cleansing composition,” if, when the composition is applied to abodily surface that has been exposed to a painful or irritatingsubstance, then removed from the bodily surface, a substantial portionof the painful or irritating substance is also removed from the bodilysurface. Without being bound by theory, compositions may cleanse abodily surface when, on application to the exposed bodily surface, thecomposition acts to dissolve or mix with the irritating or painfulsubstance without significantly penetrating the skin or other bodilysurface, and can then be removed from the bodily surface, therebyremoving a substantial portion of the painful or irritating substance.

In one aspect, the invention comprises compositions containing acomponent in which capsaicin or an analog of capsaicin is soluble; insome embodiments, the component is one in which capsaicin has a highsolubility (i.e., greater than 10% w/w, or greater than 20% w/w, greaterthan 25% w/w). Nonlimiting examples of substances in which capsaicin orits analogs may have a high solubility include lower monovalent alcohols(e.g., C₁-C₄) and low molecular weight glycols and polyols, includingpropylene glycol, polyethylene glycol (e.g., 200-600 g/mole),polypropylene glycol (e.g., 425-2025 g/mole), glycerol, butylene glycol,1,2,4-butanetriol, sorbitol esters, 1,2,6-hexanetriol, ethanol,isopropanol, butanediol, ether propanol, ethoxylated ethers,propoxylated ethers and combinations thereof.

In one embodiment the component in which capsaicin has a high solubilityis polyethylene glycol (PEG). Polyethylene glycol is an addition polymerof ethylene oxide and water, represented by the formula:H(OCH₂CH₂)_(n)OH,where n represents the average number of oxyethylene groups. There is awide variety of PEGs and derivatives thereof, and the choice of PEG,PEGs, or their derivatives to be used in the lotions of the invention ismainly driven by considerations of viscosity; the desired viscositydepends on the type of lotion, gel, cream, liniment, or spray to beformulated (see section on viscosity). Hence, suitable PEG's useful inembodiments of the invention include, for example, PEG 200-600. In someembodiments of the invention, PEG 300 is used. PEG 300 has an averagemolecular weight of 300 and average n=6. Other PEGs may be used inembodiments of the invention. Non-limiting examples include PEG 200 andPEG 400. PEG may be used that is substantially free of ethanol and/ormethanol. PEG (e.g., PEG 300) may be provided in the compositions at aconcentration of, e.g., about 60 to about 99.9 percent w/w, or about 80to about 95 percent w/w, or about 84 to about 94 percent w/w, or about87 to about 91 percent w/w, or about 89 percent w/w. Surprisingly, itwas found that PEG 300 at 90% w/w in water retains almost the samesolubility for capsaicin as pure PEG 300 (27.0% v. 27.5% solubility ofcapsaicin, respectively, see Example 2).

B. Thickener

Suitable thickeners for use in the compositions of the present inventioninclude crosslinked polyacrylate polymers, carboxylic acid polymers,polyacrylamide polymers, and mixtures thereof. Exemplary thickeners arepolymeric thickening agents including acrylic acid/ethyl acrylatecopolymers and the carboxyvinyl polymers sold by the B.F. GoodrichCompany under the trade mark of CARBOPOL resins. Such resins aredescribed in, e.g., U.S. Pat. Nos. 5,288,814 and 5,468,814, and in Amjadet al., Carbomer Resins: Past, Present and Future Cosmetics & Toiletries107 (1992), pp 81-85. These resins consist essentially of a colloidallywater-soluble polyalkenyl polyether crosslinked polymer of acrylic acidcrosslinked with from 0.75% to 2.00% of a crosslinking agent such as forexample polyallyl sucrose or polyallyl pentaerythritol. Examples includeCarbopol 934, Carbopol 940, Carbopol 950, Carbopol 980, Carbopol 951 andCarbopol 981. Also suitable for use herein are hydrophobically-modifiedcross-linked polymers of acrylic acid having amphipathic propertiesavailable under the Trade Name Carbopol 1382, Carbopol 1342 and PemulenTR-1 (CFTA Designation: Acrylates/10-30 Alkyl Acrylate Crosspolymer).Carbopol 1382 is an exemplary CARBOPOL polymer that is used in someembodiments of the invention. See, e.g., U.S. Pat. No. 6,133,212. Otheruseful crosslinked nonionic polyacrylate polymers and crosslinkedcationic polyacrylate polymers are described in U.S. Pat. Nos.5,100,660; 4,849,484; 4,835,206; 4,628,078; 4,599,379; and EP 228,868,to Farrar et al, published Jul. 15, 1987.

Other thickeners may also be used in the invention, and include acacia,agar, alginic acid, aluminum monostearate, attapulgite (activated orcolloidal activated), bentonite, purified bentonite, bentonite magma,carbomers 910, 934, 934P, 940, 941, and/or 1342, carboxymethylcellulosecalcium, carboxymethylcellulose sodium, carboxymethylcellulose sodium12, carrageenan, microcrystalline cellulose, dextrin, gelatin, guar gum,hyaluronic acid, hydroxyethyl cellulose, hydroxypropyl cellulose,hydroxypropyl methylcellulose, magnesium aluminum silicate,methylcellulose, pectin, polyethylene oxide, polyvinyl alcohol,povidone, propylene glycol alginate, silicon dioxide, colloidal silicondioxide, sodium alginate, tragacanth, xanthan gum, aluminum silicates,and other thickeners known in the art; see, e.g., U.S. Pat. No.4,387,107, Lochhead et al., Cosmetics & Toiletries 108:95-135 (1993),and USP24/NF19 U.S. Pharmcopeia/National Formulary, p. 2405 (1999).

The thickener is present in a concentration sufficient to provide properviscosity to the composition for easy application to and removal fromskin and other bodily surfaces. The viscosity provided by the thickener,in combination with the polyethylene glycol, water, and optionally othercomponents of the composition, may be in the range from, e.g., a minimumof about 100, or about 300, or about 700, or about 2000, or about 4000centipoise (cps) to a maximum of about 500, or about 700, or about 1000,or about 5000, or about 8000 cps. The desired viscosity depends on thetype of application. In some embodiments the composition comprises alotion to be applied by wiping and/or rubbing, which is preferably of aviscosity of about 4000 to about 8000 cps. In other embodiments thecomposition comprises a less viscous preparation that may be applied byspraying, which is preferably of a viscosity of about 100 to about 1000cps. Other embodiments of intermediate viscosity between spray andlotion can also be useful. The percentage of thickener in thecomposition depends on the type of PEG used (e.g., PEG 200, 300, or 400)and the percentage of PEG. The quantity of carbomer to be used isdetermined by the desired viscosity which in turn depends on theintrinsic viscosity of carbomer. The intrinsic viscosity depends onionic strength, pH, and electrolyte type present. In some embodiments, apolyacrylate polymer, for example CARBOPOL 1382™ comprises, e.g., about0.1 to about 8 percent w/w, or about 0.1 to about 2 percent w/w, orabout 0.1 to about 1.5 percent w/w, or about 0.3 to about 1.5 percentw/w, or about 1.0 percent w/w, of the composition.

C. Stabilizers

Compositions of the invention may optionally include one or morecomponents that act as stabilizers. Stabilizers useful in thecompositions are materials that aid in ensuring a stable compositionand/or prevent growth of bacteria. Measures of stability include, e.g.,maintenance of viscosity over time, maintenance of pH over time, ormaintenance of appearance, homogeneity, and/or color over time. Astabilizer may be one or more of an antioxidant, a chelator, anantibacterial, or any other agent that acts to maintain desiredcharacteristics of the composition over time. Suitable stabilizersinclude butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT),disodium edetate, methylparaben, butylparaben, propylparaben, benzylalcohol, sorbic acid, imidurea, thimerisal, propyl gallate, sodiumphosphate (monobasic and/or dibasic) and citric acid.

An example of an antioxidant for use in compositions of the invention isBHA, at about, e.g., 0.005 to about 0.1 percent w/w, or about 0.01 toabout 0.05 percent w/w, or about 0.01 to 0.03 percent w/w, or about 0.02percent w/w. Suitable chelating agents include ethylenediaminetetraacetic acid (EDTA), as EDTA disodium, calcium disodiumedetate, EDTA trisodium, EDTA tetrasodium, or EDTA dipotassium. One ormore chelating agents, e.g., EDTA disodium dihydrate, can optionally beincluded in the composition in amounts of about, e.g., 0.005 to about 1percent w/w, or about 0.02 to about 0.2 percent w/w, or about 0.1percent w/w. In some embodiments, a physiological buffer, for example,sodium phosphate, either monobasic or dibasic, or both, may be includedin the composition as a stabilizer that acts as a buffer to stabilize pHover time. For the monobasic form, amounts may be, e.g., about 0.1 toabout 1.5 percent w/w, or about 0.2 to about 1 percent w/w, or about 0.3to about 0.7 percent w/w, or about 0.5 percent w/w. For the dibasicform, amounts may be, e.g., about 0.2 to about 2 percent w/w, or about0.4 to about 1.5 percent w/w, or about 0.6 to about 1.2 percent w/w, orabout 0.8%.

Other stabilizers may optionally be added to compositions of theinvention; see, e.g., U.S. Pat. Nos. 6,013,270 and 6,390,291.

D. Water

The components of the composition are mixed with water to produce acomposition of the desired viscosity. It is generally preferred to usewater that has been purified by processes such as deionization orreverse osmosis, to improve the batch-to-batch formulationconsistencies, by reducing or eliminating dissolved solids in the watersupply. The amount of water in the composition will vary, depending onthe amounts of the other components of the composition.

E. pH Modifier

The pH of the composition affects its potential for irritation of thebodily surface to which it is applied, as well as, in some embodiments,affecting the swelling of a thickener containing carboxyl groups bydeprotonation of the carboxyl groups. If necessary, a pH modifier can beused to adjust the pH of the composition to a pH within a suitablerange. A pH modifier is a compound that will adjust the pH of acomposition to a lower, e.g., more acidic pH value, or to a higher,e.g., more basic pH value. Suitable pH modifiers include, for example,HCl, organic bases (such as triethanolamine) sodium hydroxide, potassiumhydroxide, or ammonium hydroxide. In embodiments in which the thickeningagent is a polyacrylate polymer, the pH modifier may be, for example,sodium hydroxide, to neutralize the polymer.

The composition may be at any pH that does not cause harm or irritationto the bodily surfaces to which the composition is applied in theintended manner and duration. Exemplary suitable pHs include, e.g.,between about 6.0 to about 8.0, or between about 7.0 to about 7.7, orabout 7.5.

F. Other Optional Ingredients

The compositions of the present invention may contain a wide range ofadditional, optional components. These depend on the intended use of thecomposition. For example, if the intended use includes cleansing thecul-de-sac of the eyes, the composition is preferably isotonic withrespect to the fluids of the eye and sterile. A solution that isisotonic to the eye is characterized by osmolalities of about 270 toabout 330 mOsm/kg. Osmolality of the solution of the invention may beadjusted by means of chlorides and/or bicarbonates of sodium orpotassium, sodium lactate, dextrose, and mannitol. Compositions for usein the eye may optionally include other components that arenaturally-occurring elements of the tear fluid, such as proteins,enzymes, lipids and metabolites. See, e.g., U.S. Pat. No. 4,911,933.Because the composition is applied to the eye, the composition should besterile.

Other optional components of the composition that may be added,depending on the intended use, include, e.g., surfactants, naphthol soap(available commercially as FELS-NAPTHA™), a cooling agent, a fragrancecomponent, a skin soothing or skin healing agent, and/or polyethylenegranules to assist the composition in reaching irregularities of theskin (used, e.g., to assist in removal of irritating substances from theskin, such as urushiols from poison oak, ivy, and sumac). Surfactantsinclude, e.g., sodium lauryl sarcosinate, sodium lauryl sulfate,nonoxynol 9, and other long-chain surfactants. Examples of coolingagents useful for the present invention include menthols, menthyllactate, menthyl glycerol, menthyl salicylate, menthone glycerineacetal, alcohol, and borneols such as l-menthol, dl-menthol, d-camphor,dl-camphor, d-bomeol and dl-borneol. Plant extracts containing one ormore of these compounds, for example, peppermint oil, peppermintextract, Perilla frutescens Britton var. acuta Kudo extract, camphortree extract and lavender extract, may also be used. Examples of otheruseful cooling agents include asymmetrical carbonates, thiocarbonatesand urethanes, N-substituted carboxamides, ureas or phosphine oxides, asdescribed in J. Cosmet. Chem., vol. 29, p. 185 (1978). These coolingagents may be used either singly or in any combination thereof. Thecooling component is preferably incorporated into the composition in aproportion of from about 0.001, 0.005, 0.02, 0.05, 0.1, 0.5, 2, 3, 4, 5,6, 7, 8, 9, or 10% by weight, to about 0.005, 0.02, 0.05, 0.1, 0.5, 2,3, 4, 5, 6, 7, 8, 9, 10, 12 or 14% by weight. Cooling agents are furtherdescribed in, e.g., U.S. Pat. Nos. 6,277,385 and 6,203,804. Fragrancesare aromatic substances which can impart an aesthetically pleasing aromato compositions of the invention. Typical fragrances include aromaticmaterials extracted from botanical sources (e.g., rose petals, gardeniablossoms, jasmine flowers, etc.) which can be used alone or in anycombination to create essential oils. One or more fragrances canoptionally be included in the composition in an amount ranging fromabout 0.001, 0.005, 0.02, 0.05, 0.1, 0.5, 2, 3, or 4% by weight to about0.005, 0.02, 0.05, 0.1, 0.5, 2, 3, 4, or 5% by weight. Fragrance agentsare further described in, e.g., U.S. Pat. No. 6,428,772. Thecompositions of the present invention may further comprise a skinsoothing or skin healing component. Skin soothing or skin healingcomponents suitable for use herein include, e.g., panthenoic acidderivatives (including, e.g., panthenol, dexpanthenol, ethyl panthenol),aloe vera, allantoin, bisabolol, and dipotassium glycyrrhizinate. Theskin soothing or skin healing agent may be added to the presentcomposition in a proportion from about 0.05, 0.1, 0.5, 2, 3, 4, 5, 7,10, 15, 20, or 25% by weight to about 0.1, 0.5, 2, 3, 4, 5, 7, 10, 15,20, 25, or 30% by weight. The CTFA Cosmetic Ingredient Handbook, SeventhEdition, 1997 and the Eighth Edition, 2000, describe a wide variety ofother cosmetic and pharmaceutical ingredients commonly used in skin carecompositions that are suitable for use in the compositions of thepresent invention. Examples of these functional classes disclosed inthis reference include: absorbents, abrasives, anticaking agents,antifoaming agents, binders, biological additives, buffering agents,bulking agents, chemical additives, colorants, fragrance components,humectants, opacifying agents, plasticizers, propellants, reducingagents, skin-conditioning agents (emollient, humectants, miscellaneous,and occlusive), skin protectants, solubilizing agents, and suspendingagents (nonsurfactant).

G. Combinations

Exemplary combinations of components for cleansing compositions include,for example, compositions containing polyethylene glycol, a thickeningagent, and water, where the composition may contain, e.g., about 60 toabout 99 percent w/w polyethylene glycol (PEG, e.g., PEG 300); about 0.1to about 4 percent w/w polyacrylate thickening agent; and the balancewater; where the composition is at a pH between about 6.0 and about 8.0.Another example of a combination that may be used in the invention is acombination containing about 84 to about 94 percent w/w PEG (e.g., PEG300); about 0.1 to about 2 percent w/w polyacrylate thickening agent;and the balance water; where the composition is at a pH of about 7.0 toabout 7.7. The latter composition may further contain stabilizer; forexample, about 0.005 to about 0.05 percent w/w butylated hydroxyanisole;and about 0.05 to about 0.5 percent w/w EDTA/EDTA salts. In anotherembodiment, the composition may contain about 87 to about 91 percent w/wPEG (e.g., PEG 300); about 0.3 to about 1.5 percent w/w polyacrylatethickening agent; about 0.01 to about 0.03 percent w/w butylatedhydroxyanisole; about 0.02 to about 0.2 percent w/w EDTA/EDTA salts; andabout 9 to about 13 percent w/w water; where the composition is at a pHof about 7.0 to about 7.7. In a further embodiment, the composition maycontain about 89.08 percent w/w PEG 300; about 1.0 percent w/wpolyacrylate thickening agent; about 0.02 percent w/w butylatedhydroxyanisole; about 0.1 percent w/w disodium edetate; and the balancewater; where the composition is at a pH of about 7.5. In a furtherembodiment, the composition is about 87 to about 91 percent w/w PEG(e.g., PEG 300); about 0.3 to about 1.5 percent w/w polyacrylatethickening agent; about 0.01 to about 0.03 percent w/w butylatedhydroxyanisole; about 0.02 to about 0.2 percent w/w EDTA/EDTA salts; andabout 9 to about 13 percent w/w water; where the composition is at a pHof about 7.0 to about 7.7.

H. Containers and Packaging for the Composition

The composition may be provided in any suitable container known in theart or apparent to the ordinarily skilled artisan. Exemplary containersfor the composition include towels or towellettes in which thecomposition is impregnated or dispersed, or containers holding thecomposition and from which the composition may be dispensed. Suchcontainers may comprise elements for convenient dispensing of thecomposition, such as described in, e.g., U.S. Pat. No. 6,013,270. Insome embodiments the composition may be provided impregnated in a poroussubstrate (e.g., towellette), such as described in, e.g., U.S. Pat. No.6,015,763. The container may be further contained in suitable packaging.

In some embodiments of the invention the composition is provided in acontainer, and optionally further packaging, and a set of instructionsfor use of the composition to remove irritating substances, e.g.,capsaicin, from the skin is also included. The instructions may be inany form, and provided, e.g., as a separate insert or on a label that isaffixed to the container or packaging. Exemplary additional componentsinclude chemical-resistant disposal bags, applicators for applying thecleansing composition, towels or towellettes for the capsaicin cleansinglotion, diluent, gloves, eye protection, scissors, marking pens, andadditional bodily surface-cleansing agents such as alcohol swabs.

II. KITS OF THE INVENTION

In an aspect, the present invention provides a kit including acomposition comprising capsaicin (or capsaicin analog) and a compositionin which capsaicin (or capsaicin analog) is soluble to at least about10% w/w, or at least about 20% w/w, or at least about 25% w/w. In someembodiments, a kit of the invention include a capsaicin cleansingcomposition described above. Optionally, a third composition comprisingan anesthetic may also be provided. The kits of the present inventionmay further comprise suitable packaging of the respective compositions,instructions, and/or other optional components as disclosed below.

A. Composition Comprising Capsaicin or a Capsaicin Analog.

The kits provided herein comprise a composition containing capsaicin ora capsaicin analog.

Capsaicin and its analogs are used both as irritants (e.g., peppersprays) and in preparations for the relief of pain. Capsaicinselectively modulates sensory nerve fibers in such a way as to activate,then desensitize, nociceptors in peripheral tissues. Analogs ofcapsaicin with physiological properties similar to capsaicin may also beused in the kits provided herein; exemplary analogs of capsaicin arenonivamide, capsaicin isomers, and dihydrocapsaicin, described in, e.g.,Govindarajan and Sathyanrayana, Crit Rev Food Sci Nutr 29:435-474(1991); U.S. Pat. Nos. 5,290,816; 4,812,446; and 4,424,205; and Ton etal., Brit J Pharmacol, 10:175-182 (1955). Topical application ofcapsaicin and capsaicin analogs for pain relief is described in U.S.Pat. Nos. 6,239,180 and 6,248,788.

Kits of the invention may include a composition comprising capsaicin ora capsaicin analog in a wide variety of concentrations. These include,e.g., about 0.001 to about 60% by weight, for example, about 0.001 toabout 1% by weight; or about 0.05% to about 15% by weight, or about 1%to about 10% by weight, or about 5% to about 10% by weight, or about7.5% by weight. When supplied as a dermal patch (below), the capsaicinor capsaicin analog may be present at, e.g., about 0.01 mg/cm² to about1 mg/cm², or about 0.1 to about 1 mg/cm², or about 0.3 to about 0.9mg/cm², or about 0.64 mg/cm².

The capsaicin or capsaicin analog composition of the kits includes avehicle suitable for topical or dermal application, for example (but notlimited to) those described in U.S. Pat. Nos. 6,239,180 and 6,248,788.These patents disclose high concentration (e.g., >5% w/w) capsaicin orcapsaicin analog compositions (including dermal patches) for topicalapplications, wherein the capsaicin may be in a vehicle such as alotion, e.g. velvachol (available from Galderma USA) and EUCERIN™. Inthe case of a patch, the capsaicin is contained in a vehicle comprisinga skin penetrating lotion or dispersed in a vehicle comprising apolymeric matrix, or mixed directly with a vehicle that also serves asadhesive for the patch. Other methods for the construction and uses oftransdermal patches may be found in, e.g., Drug Delivery SystemsCharacteristics and Biomedical Application, R. L. Juiano, ed., OxfordUniversity Press, N.Y. (1980); and Controlled Drug Delivery, Vol. IBasic Concepts, Stephen D. Bruck (1983).

The capsaicin or capsaicin analog and vehicle may be further packaged inany suitable packaging for segregation from other components of the kitand to facilitate dispensing of the composition.

B. Cleansing Composition.

The cleansing composition of the kits may be a composition in whichcapsaicin is soluble to at least about 10% w/w, or at least about 20%w/w, or at least about 25% w/w; e.g., any of the capsaicin cleansingcompositions described herein. The composition may be provided in anysuitable container, as described previously. The container may compriseelements for convenient dispensing of the cleansing composition, such asdescribed in, e.g., U.S. Pat. No. 6,013,270. In some embodiments thecleansing composition may be provided impregnated in a porous substrate,such as described in, e.g., U.S. Pat. No. 6,015,763. The container maybe further packaged in any suitable packaging for segregation from othercomponents of the kit and to facilitate dispensing of the cleansingcomposition.

C. Anesthetic.

The kits of the invention may optionally further include an anestheticcomposition. Burning pain and hyperalgesia to both heat and touchtypically occur after applications of even the relatively lowconcentration capsaicin ointments known to the art. Such burning painmay be avoided by first administering an anesthetic, so as to causeregional anesthesia in the areas to be treated. Exemplary regionalanesthetic agents that may be used in the anesthetic compositionsoptionally included in the kits of the invention are sodium channelblockers. A variety of sodium channel blocking anesthetics are known anduseful, such as lidocaine, tetracaine, bupivicaine and chloroprocaine.The suitable anesthetic may be contained in a vehicle such as lotion orgel (see description for capsaicin compositions) or as a patch device(see description for capsaicin compositions). Anesthetics for use withcapsaicin compositions are further described in U.S. Pat. Nos. 6,239,180and 6,248,788.

The anesthetic and vehicle may be further packaged in any suitablepackaging for segregation from other components of the kit and tofacilitate dispensing of the composition.

D. Instructions.

Kits of the invention may further include instructions for use of thecleansing composition. Instructions may be included as a separate insertand/or as part of the packaging or container, e.g., as a label affixedto a container or as writing or other communication integrated as partof a container. The instructions may inform the user of methods forapplication and/or removal of the cleansing composition, precautions andmethods concerning handling of material contaminated with an irritatingor painful substance, expected results, warnings concerning improperuse, and the like.

E. Additional Optional Components of the Kits of the Invention.

Kits of the present invention may further contain components useful inthe application and removal of capsaicin or capsaicin analogs. Exemplaryadditional components include chemical-resistant disposal bags,applicators, bodily surface-cleansing agents such as alcohol swabs,diluent, towels or towellettes for wiping excess cream prior to the useof the capsaicin cleansing lotion and for wiping cleansing lotion,gloves, scissors, marking pens and eye protection.

III. MAKING CLEANSING LOTIONS

One method for making some embodiments of the cleansing lotions providedby the present invention is shown in FIG. 1. PEG, water, and (if used)stabilizers such as BHA and/or EDTA and/or sodium phosphate, arecombined in a manufacturing vessel and mixed until dissolved. Thethickening agent, e.g., CARBOPOL 1382, is added to the mixture anddispersed, and mixing is continued until the polymer is properlyhydrated. Then, if necessary, a pH modifier, e.g., 10% sodium hydroxidesolution, is added and mixing is continued until a gel is formed.

IV. METHODS OF THE INVENTION

The invention also provides methods for using the compositions and kitsof the invention. In one embodiment, the invention provides a method forcleansing a bodily surface that has been contacted with an irritating orpainful substance (e.g., capsaicin or a capsaicin analog, or aurushiol). Bodily surfaces to be treated may include skin, eyes, mucousmembranes, hair, and, in the case of animals, fur (e.g., to cleanse ananimal that has come into contact with an irritating, painful, ornoxious substance). The bodily surface is cleansed by applying to thebodily surface a cleansing composition containing polyethylene glycol, athickening agent, and water, then removing the composition from thebodily surface. Any of the compositions described herein may be used inthe methods. In one embodiment, the cleansing composition may contain,e.g., about 80 to about 99 percent w/w polyethylene glycol; about 0.1 toabout 2 percent w/w polyacrylate thickening agent; and about 1 to about20 percent w/w water; where the composition is at a pH of about 7.0 toabout 7.7. In another embodiment, the cleansing composition may containabout 87 to about 91 percent w/w polyethylene glycol; about 0.3 to about1.5 percent w/w polyacrylate thickening agent; about 0.01 to about 0.03percent w/w butylated hydroxyanisole; about 0.02 to about 0.2 percentw/w EDTA/EDTA salts; and about 9 to about 13 percent w/w water; wherethe composition is at a pH of about 7.0 to about 7.7; then removing thecomposition from the bodily surface.

Methods of the invention also include methods for treating an individualsuffering from a capsaicin-responsive condition with the kits of theinvention. For illustration and not limitation, capsaicin-responsiveconditions include neuropathic pain (including pain associated withdiabetic neuropathy, postherpetic neuralgia, HIV/AIDS, traumatic injury,complex regional pain syndrome, trigeminal neuralgia, erythromelalgiaand phantom pain), pain produced by mixed nociceptive and/or neuropathicmixed etiologies (e.g., cancer, osteoarthritis, fibromyalgia and lowback pain), inflammatory hyperalgesia, vulvar vestibulitis orvulvodynia, interstitial cystitis, neurogenic or overactive bladder,prostatic hyperplasia, rhinitis, rectal hypersensitivity, burning mouthsyndrome, oral mucositis, herpes (or other viral infections), prostatichypertrophy, dermatitis, pruritis, itch, tinnitus, psoriasis, warts,cancers (especially skin cancers), headaches, and wrinkles. As usedherein, an “individual” is a vertebrate; e.g., a mammal; e.g., a human.The condition is treated by applying a composition comprising capsaicinor a capsaicin analog (as described above) to the area affected by thecondition, then cleansing the area with a cleansing composition of theinvention. The capsaicin may be administered in any number of ways,e.g., in a lotion, cream, emulsion, liniment, spray, transdermal patch,gel, or the like. The method may further include administering ananesthetic prior to the application of the capsaicin-containingcomposition, for example administering an afferent nerve fiber blockingregional anesthetic to the affected area. In one embodiment, thecomposition comprising capsaicin or a capsaicin analog may be containedin a transdermal patch. In such embodiments, the capsaicin cleansingcomposition may be used to cleanse areas around the patch after it hasbeen affixed as well as any areas inadvertently exposed to capsaicin; inaddition the capsaicin cleansing composition may be used to cleanse thearea to which the patch was affixed, after removal of said patch. Forcleansing the area after application of a patch and the removal of thepatch, for example, a tube containing 50 gm of cleansing gel may beapplied to a site following removal of capsaicin patch, e.g., an 8%capsaicin patch. The cleansing gel is left on the area for a period oftime sufficient to allow capsaicin to be removed from the bodily surfaceto the gel, for example, for one minute, and then wiped off with drygauze or dry paper towels. Upon removal from the treated area, all usedgauze, paper towels or other materials placed in contact with thetreated area are immediately disposed of in a plastic biohazard bag,which is then closed and sealed.

In some embodiments, the patch includes a reservoir containing atherapeutic formulation where the formulation is provided to the surfaceof the skin, and where the formulation comprises capsaicin or acapsaicin analog in a total concentration from greater than about 5% byweight of the formulation. In some embodiments, the capsaicinconcentration is less than or equal to about 5% by weight of thecomposition.

V. EXAMPLES Example 1

Several substances were evaluated for their ability to dissolvecapsaicin. The solubility of capsaicin in different solvents wasdetermined by exposing the sample to 90 minutes of sonication andallowing the water-bath temperature increase to approximately 40° C.Physical evaluation (i.e., visual) was conducted on the sample todetermine solubility. The solubility of capsaicin in these substances isshown in Table 1.

TABLE 1 Solubility of capsaicin in various substances Solvent CapsaicinSolubility (% w/w) Mineral Oil <1.0 Isopropyl Myristate <5.2Octyldodecanol <5.2 Peanut Oil <3.6 Soybean Oil <3.5 Oleyl Alcohol15.1-22.0 Propylene Glycol 23.4-26.3 Ethanol, 95% >50 PEG 300 21.0-23.0Triacetin  5.0-10.1 Ethoxydiglycol >50

The results of this Example show that capsaicin has a high solubility inPEG 300, which also has low irritation potential and is compatible witha variety of excipients.

Example 2

In this example, the solubility of capsaicin in three different forms ofPEG and in PEG of different concentrations was tested. The mixtures weresonicated for two hours and allowed to reach ambient conditions. Sampleswere then centrifuged and filtered prior to being analyzed by HPLC. Thesolubility of capsaicin in three different molecular weight PEGs, and indifferent concentrations of PEG 300 in water, is shown in Table 2.

TABLE 2 Polyethylene Glycol Capsaicin Solubility (% w/w) PEG 200 27.0PEG 300 27.5 PEG 400 22.0 PEG 300/H₂O (80/20) 12.5 PEG 300/H₂O (90/10)27.0

Of the PEG's tested, PEG 300 has the greatest capacity for capsaicin,with a capsaicin solubility of 27.5% w/w. 90% PEG 300 has a greatersolubility for capsaicin than 80% PEG 300 (27.0% vs. 12.5%,respectively). Capsaicin is also quite soluble in PEG 200, at 27%.

Example 3

In this example, formulations were prepared using various pH modifiersand with or without BHA and/or EDTA, or sodium phosphate, and theirstabilities were followed over time at three different temperatures.Stability was assessed by evaluating appearance, pH, and viscosity. Theformulations used are presented in Table 3.

TABLE 3 Formulations tested for stability % (w/w) Component 43A 43B 44A44B 45A 54A 54B PEG 300 89.2 79.2 89.2 88.85 89.1 89.18 89.08 CARBOPOL1382 0.5 0.5 0.5 0.75 0.5 0.5 0.5 Sodium Hydroxide 0.03 0.03 — 0.04 0.030.03 0.03 50% Trolamine Soln. — — 0.3 — — — — BHA — — — — 0.1 0.02 0.02Disodium Edetate — — — — — — 0.1 Purified Water qwad 100 100 100 100 100100 100

Stability data are presented in Table 4 (pH's are lower than theformulated pH's because the samples were diluted 1:9 with water). Themethod of preparation is shown in FIG. 1.

TABLE 4 Stability data for various formulations Test Viscosity % BatchStorage pH From No.: Condition Time Appearance (1:9) cps Initial 790- 5° C. Initial Clear - 5.3 5,000 100  43A Slightly Hazy Gel 2 WeeksConforms 5.2 N.T — 1 Month Conforms 5.2 N.T — 3 Months Conforms N.T N.T— 25° 2 Weeks Conforms 5.3 N.T — 1 Month Conforms 5.2 5,300 110  3Months Conforms 5.0 2,800 56 40° 2 Weeks Conforms 5.0 4,300 86 1 MonthConforms 4.9 2,600 52 2 Months Conforms N.T 2,300 46 3 Months Conforms4.5 2,400 48 790-  5° C. Initial Clear - 5.1 6,700 100  43B SlightlyHazy Gel 2 Weeks Conforms 5.1 N.T — 1 Month Conforms 5.2 N.T — 3 MonthsConforms N.T N.T — 25° 2 Weeks Conforms 5.1 N.T — 1 Month Conforms 5.05,500 82 3 Months Conforms 4.9 4,800 72 40° 2 Weeks Conforms 5.1 5,30079 1 Month Conforms 4.9 2,900 43 2 Months Conforms N.T 2,000 30 3 MonthsConforms 4.2 1,800 27 790-  5° C. Initial Clear - 5.6 3,600 100  44ASlightly Hazy Gel 2 Weeks Conforms 5.6 N.T — 1 Month Conforms 5.5 N.T —3 Months Conforms N.T N.T — 25° 2 Weeks Conforms 5.5 N.T — 1 MonthConforms 5.5 3,500 97 3 Months Conforms 5.2 3,200 89 40° 2 WeeksConforms 5.2 4,800 133  1 Month Conforms 5.3 3,000 83 2 Months ConformsN.T 1,500 42 3 Months Conforms 4.7 1,700 47 790-  5° C. Initial Clear -Slightly 5.2 10,600  100  44B Hazy Gel 2 Weeks Conforms 5.0 N.T — 1Month Conforms 5.0 N.T — 3 Months Conforms N.T N.T — 25° 2 WeeksConforms 4.8 N.T — 1 Month Conforms 5.0 9,300 88 3 Months Conforms 4.96,300 59 40° 2 Weeks Conforms 4.9 10,300  100  1 Month Conforms 4.77,500 71 2 Months Conforms N.T 4,800 45 3 Months Conforms 4.2 5,300 50790-  5° C. Initial Clear - Slightly 5.2 4,300 100  45A Hazy Gel 2 WeeksConforms 5.1 N.T — 1 Month Conforms 5.1 N.T — 3 Months Conforms N.T N.T— 25° 2 Weeks Conforms 5.2 N.T — 1 Month Conforms 5.1 4,900 114  3Months Conforms 5.1 3,800 88 40° 2 Weeks Conforms 5.0 4,300 100  1 MonthConforms 4.9 4,100 95 2 Months Conforms N.T 2,800 65 3 Months Conforms4.7 2,300 53 790-  5° C. Initial Clear - Slightly 5.3 6,500 100  54AHazy Gel 2 Weeks Conforms N.T N.T — 1 Month Conforms N.T N.T — 3 MonthsN.T N.T N.T — 25° 2 Weeks Conforms N.T N.T — 1 Month Conforms 5.2 4,70072 3 Months Conforms 5.2 5,000 77 40° 2 Weeks Conforms 5.2 6,800 105  1Month Conforms 5.1 5,500 85 1.5 Months Conforms N.T 5,500 85 3 MonthsConforms 5.1 4,800 74 790-  5° C. Initial Clear - Slightly 5.2 4,750100  54B Hazy Gel 2 Weeks Conforms N.T N.T — 1 Month Conforms N.T N.T —3 Months N.T N.T N.T — 25° 2 Weeks Conforms N.T N.T — 1 Month Conforms4.9 4,700 99 3 Months Conforms 5.0 4,500 95 40° 2 Weeks Conforms 5.15,000 105  1 Month Conforms 5.1 4,250 89 1.5 Months Conforms N.T 4,00084 3 Months N.T N.T N.T — N.T. = not tested

This Example shows that several formulations are stable over time,especially those containing both BHA and EDTA, e.g., sample 790-54B.

Example 4

To determine the ability of cleansing gel to remove irritable substancesfrom surfaces, a range of concentration of capsaicin solutions, in avolatile solvent, were applied to stainless steel coupons. Thin films ofcapsaicin (ranging from 4 μg to 16 μg per centimeter square) remainingon the surface of the steel coupons were equivalent to the maximumanticipated amount of capsaicin left on skin following clinicalapplications of 8% by weight capsaicin patches. The amount of cleansinggel used per square centimeter of surface, and application time wereadapted from the clinical experience of cleansing gel usage.

Preparation of Capsaicin Solutions

A stock solution of capsaicin, in methanol, containing 103.1 mg/100 mLcapsaicin ((Lot F0010103) Formosa Laboratories, Taiwan) in a 100-mLvolumetric flask, was prepared. The solution was clear and colorless. 10mL each of four concentrations of capsaicin solutions 0.4 mg/mL, 0.3mg/mL, 0.2 mg/mL and 0.1 mg/mL were prepared from above stock solution.

Cleaning of Steel Coupons Exposed to Capsaicin Solutions

Four steel coupons, 5 cm×5 cm each, (316 SS Finish from Globe Pharma)were rinsed with methanol and allowed to dry completely. 1 mL of 0.1mg/mL capsaicin solution was slowly applied to a coupon at about 40° C.(on a hot plate) such that methanol evaporated without solutiondribbling from the edges.

For these experiments, a cleansing gel with the following components wasused:

Component % (w/w) Carbowax PEG 300 (Polyethylene 89.08 Glycol 300)Carbopol 1382 1.00 Versene NA (Edetate Disodium) 0.10 Sodium Hydroxide,10% solution 0.30 Butylated Hydroxyanisole 0.02 Purified Water 9.50

The dried coupon was smeared with 1 mL of cleansing gel which wasremoved after one minute with a single pre-washed swab (which was alsoused to apply cleansing gel). The collected gel along with the swab wasadded to a pre-washed scintillation vial containing a small magneticstirrer. 9 mL methanol was added and the sample was stirred for 10minutes. Three more samples were prepared in similar fashion using 0.4mg/mL, 0.3 mg/mL and 0.2 mg/mL capsaicin solutions. TABLE 5 describesthe percent capsaicin recovery from four samples containing differentinitial capsaicin amounts.

TABLE 5 Percent Recovery of Capsaicin Capsaicin Amount Amount UVConcentration Capsaicin Capsaicin Percent Sample ID Absorbance Adjustedof Recovered Recovered³ Applied⁴ Capsaicin (mg/mL) at 281 nm Absorbance¹Solution² (mg) (mg) Recovery 0.10 0.212 0.156 0.011769 0.11769 0.1 117.70.20 0.261 0.205 0.016818 0.16818 0.2 84.1 0.30 0.302 0.246 0.0210420.21042 0.3 70.1 0.40 0.415 0.359 0.032684 0.32684 0.4 81.7 ¹AdjustedAbs. = Abs − subtraction factor (0.056) ²Concentration = (Adjusted Abs.− Y intercept)/slope [from linear curve in FIG. 2] ³Amount Recovered =Concentration × vol of solution containing recovered gel (i.e. 10 mL)⁴Amount of capsaicin in one mL of application solution

As the results in Table 3 indicate, the cleansing gel achieved anaverage of 88.4% capsaicin recovery. In the case of 0.1 mg/mL capsaicinconcentration, experimental error appears to have led to a higher number(i.e. 117.7%). Exclusion of this data point shifts the average percentrecovery down to 78.6% removal of residual amounts of capsaicin from aninert surface.

Example 5

This example describes the preparation of cleansing gels containingmenthol as a cooling agent.

Cleansing gel formulations containing 1% L-menthol were prepared bycombining 1.20 g of L-menthol (Spetram RL 1492) with 118.8 g ofcleansing gel, mixing it overnight and additionally for 1 hour in asteam bath. The resulting formulation was a colorless gel with smallamount of white solids, a characteristic odor of menthol, and aviscosity of 7,250 cps.

Cleansing gel formulations with 3% L-menthol were prepared by combining3.61 g of L-menthol (Spetram RL 1492) with 116.41 g of cleansing gel,mixing it overnight and additionally for 1 hour in a steam bath. Theresulting formulation was a colorless gel with medium amount of whitesolids, a characteristic odor of menthol, and a viscosity of 6,500 cps.

Cleansing gel formulations with 10% L-menthol were prepared by combining1.20 g of L-menthol (Spetram RL 1492) with 118.8 g of cleansing gel,mixing it overnight and additionally for 1 hour in a steam bath. Theresulting formulation was a colorless gel with white solids, acharacteristic odor of menthol, and a viscosity of 4,750 cps.

Example 6

This example describes the lack of skin penetration of polyethyleneglycols that make up PEG 300.

PEG 300 is a polymer of ethylene glycol. The molecular weight ofpolymers is reported as an average of all constituting fractions. PEGhas an average molecular weight of 300. PEG 300 was analyzed to detectand estimate polymer units with 5 to 8 monomer units the molecularweights of which constitute a range centered on 300 (i.e. PEG 239, PEG283, PEG 327, and PEG 371). As expected these molecules were abundant inthe cleansing compositions provided by the present invention, asdetermined by LC-MS, and were used as representative molecules in thisExample.

The cleansing gel described in Example 4 was placed on human cadaverskin that was mounted on an O-ring and placed between the donor andreceiver chambers of a Franz diffusion cell. The penetration of the fourcomponents across the skin was investigated over a three-hour period.These results were compared to those for caffeine, a reference compoundfor high permeation, and atenolol, a reference compound for lowpermeation. Table 6 provides the skin permeability coefficients (Papp)for the monitored components of the cleansing gel composition and thetwo reference compounds. Donor #1 was untreated skin. Donor #2 was skintreated with an 8% capsaicin composition for 60 minutes.

TABLE 6 Permeability of skin to PEG, caffeine, and atenolol Papp (cm/hr)Compound Donor #1 Donor #2 PEG 239 0.5 × 10⁻⁷ 2.8 × 10⁻⁷ PEG 283 0.5 ×10⁻⁷ 2.0 × 10⁻⁷ PEG 327 0.5 × 10⁻⁷ 1.9 × 10⁻⁷ PEG 371 0.5 × 10⁻⁷ 1.5 ×10⁻⁷ Caffeine 3.0 × 10⁻⁴ 5.1 × 10⁻⁴ Atenolol 1.9 × 10⁻⁵ 3.6 × 10⁻⁵

The Papp of each of the four main components of the cleansing gel wassignificantly lower than the low permeability reference, indicating thatthe permeability of skin to the polyethylene glycol components of thecleansing gel is exceptionally low, e.g., having a Papp of not greaterthan 1×10⁻⁶, or 5×10⁻⁷ cm/hr.

It is understood that the examples and embodiments described herein arefor illustrative purposes only and that various modifications or changesin light thereof will be suggested to persons skilled in the art and areto be included within the spirit and purview of this application andscope of the appended claims. All publications, patents and patentapplications cited herein are hereby incorporated by reference in theirentirety for all purposes to the same extent as if each individualpublication, patent or patent application were specifically andindividually indicated to be so incorporated by reference.

The invention claimed is:
 1. An aqueous composition for cleansingcapsaicin from a bodily surface comprising: a) about 80 to about 99percent w/w polyethylene glycol (PEG); and b) about 0.1 to about 4.0percent w/w polyacrylate thickening agent, wherein the aqueouscomposition has a viscosity of between 100 to 8000 cps.
 2. The aqueouscomposition of claim 1, comprising: about 84 to about 94 percent w/wpolyethylene glycol (PEG).
 3. The aqueous composition of claim 2,further comprising a stabilizer.
 4. The aqueous composition of claim 3,further comprising a cooling agent.
 5. The aqueous composition of claim3, comprising: a) about 87 to about 91 percent w/w polyethylene glycol(PEG); b) about 0.3 to about 2 percent w/w polyacrylate thickeningagent; c) about 0.01 to about 0.03 percent w/w butylated hydroxyanisole;d) about 0.02 to about 0.2 percent w/w edetate sodium; and e) thebalance water; wherein the aqueous composition is at a pH of about 7.0to about 7.7.
 6. The aqueous composition of claim 5, comprising: a)about 89.08 percent w/w PEG 300; b) about 1.0 percent w/w polyacrylatethickening agent; c) about 0.02 percent w/w butylated hydroxyanisole; d)about 0.1 percent w/w disodium edetate; and e) the balance water;wherein the aqueous composition is at a pH of about 7.5.
 7. The aqueouscomposition of claim 1, having a pH between about 7.0 and about 7.7. 8.The aqueous composition of claim 2, comprising about 90 percent w/wpolyethylene glycol (PEG).
 9. The aqueous composition of claim 8,further comprising: i) about 0.1 to about 2.0 percent w/w polyacrylatethickening agent; and ii) the balance water; wherein the aqueouscomposition is at a pH between about 7.0 and about 7.7.
 10. The aqueouscomposition of claim 1, wherein the PEG is PEG 200 to PEG
 600. 11. Theaqueous composition of claim 1, in which capsaicin has a solubility ofat least about 10 to 25 percent w/w.
 12. The aqueous composition ofclaim 11, in which capsaicin has a solubility of about 10 percent w/w.13. The aqueous composition of claim 11, in which capsaicin has asolubility of about 20 percent w/w.
 14. The aqueous composition of claim11, in which capsaicin has a solubility of about 25 percent w/w.
 15. Theaqueous composition of claim 1, which is a surfactant-free gel.
 16. Theaqueous composition of claim 1, wherein the viscosity is between 4000cps to 8000 cps.
 17. The aqueous composition of claim 16, wherein theviscosity is between 4000 to 5000 cps.
 18. The aqueous composition ofclaim 1, wherein the viscosity is between 2000 to 5000 cps.
 19. Theaqueous composition of claim 1, wherein the viscosity is between 100 to1000 cps.
 20. The aqueous composition of claim 1, which is substantiallyfree of particulates.
 21. The aqueous composition of claim 1, whereinthe polyacrylate thickening agent is an acrylic acid/ethylacrylatecopolymer or a carboxyvinyl polymer.